The objective of this proposal is to evaluate the pharmacokinetic parameters and possible toxic effects of different doses of aminopterin with citrovorum factor "rescue" in cancer patients. This study will determine the maximum tolerated dose of the drug (with minimal toxicity in the presence of citrovorum factor "rescue", alkalinization of urine and ample fluid intake). Attempts will be made to correlate a) dose with plasma levels of the drug, b) plasma level (and/or dose) with toxicity, c) plasma level (and/or dose) and efficacy of the drug, d) renal function with renal clearance of the drug, e) renal clearance or total body clearance with toxicity. Patients with neoplastic disease who fit the criteria for selection and qualify for this study (after preliminary tests) will be given aminopterin as a single i.v. bolus with prior alkalinization of urine (p.o. NaHCO3) and hydration. Three patients will receive 25 mg/m2 of aminopterin, followed at 24 hours by 2o mg i.v. of cirtovorum factor and then 5 mg every 6 hours for 10 doses. Other patients in groups of three will then receive higher doses (50, 100, 150, 200 mg/m2, etc.) with appropriate doses of citrovorum factor. The highest dose of aminopterin employed will depend upon the appearance of toxic symptoms. When a dose level is reached which can be tolerated without much toxicity, three additional patients will receive that dose. Blood and urine will be obtained at pre-determined intervals, other biological materials such as bile, cerebrospinal fluid, bone marrow aspirate, biopsy tissues, etc., will be obtained if available. Aminopterin levels will be measured in these biological materials by a sensitive radioimmunoassay developed by us. The binding of aminopterin to plasma proteins will be measured by equilibrium dialysis. Complete blood count, platelet count and urinalyses will be carried out. Toxic manifestations and/or kinetic parameters will be determined for aminopterin in plasma, blood and urine. Any relationship between clinical and/or toxicological findings with pharmacokinetic data will be evaluated. Then, additional studies with different protocols (e.g., continuous infusion) will be carried out.